We know quite a bit more about the Nature papers on stress-induced STAP stem cells than we did just a couple weeks ago when they were published, but there are many crucial outstanding questions too and odd things that remain unresolved. Below are my top STAP stem cell oddities.

10. Dr. Vacanti says that STAP stem cells are probably the same as “spore stem cells”, a controversial possible type of Vacanti lab described ultra-tiny, ultra-tough kind of stem cell in spore-like form that can be as small as 1 micron. I still cannot wrap my head around the idea that STAP and spore stem cells are the same given what seem to me to be stark differences.

9. A controversial 2011 Obokata and Vacanti Tissue Engineering paper contains apparent numerous, serious image duplications/inversions. Does this connect to the Nature STAP papers, which have at least one image duplication as well? Will the Tissue Engineering paper be retracted?

8. Then there is also a duplicated placenta image in two different figures in one of the Nature STAP papers. It wasn’t even clear to me that those individual embryo/placenta figure panels were actually each overlays of multiple distinct images. Seems strange.

7. Post-publication of the STAP papers Nature did asurvey of leading stem cell labs about the reproducibility of the STAP method described in its own published papers on STAP. That seems like a remarkable decision by a major journal.

6. Why didn’t the STAP authors follow Nature policy and deposit their data into an open database such as GEO before publication? Why is this only going to happen much later, perhaps weeks from now? Why didn’t Nature editors catch this issue pre-publication?

5. AVacanti lab member, self-identified as a lab tech but without a specific name, goes on Reddit chatting about STAP shortly after the paper comes out. What the heck? This person goes by the name “Thyferra2680” on Reddit. Who is s/he? Are they really a member of that lab? The full comment exchange can be found here. Here’s an example of one of Thyferra2690’s comments:

This is a huge deal for our lab! It’s a paper in Nature (which doesn’t fuck around with their publications) and it’s a completely brand new method of creating stem cells. It could lead to all sorts of new collaborations and people interested in the lab.

and also s/he said on high efficiency:

I don’t know if it’s just luck, but I’ve made STAPs just about every single time I’ve treated them….

4. Apparently the Vacanti lab, at least according to the lab tech on Reddit, does not even generally use the “acid bath” approach to make its STAP stem cells. It perhaps uses some other, agitation-based stress method? The supposed Vacanti tech said on Reddit: “A lot of people are asking me about the acid and the low pH method of creating STAPs. I’ll be completely honest, I don’t use the acid method.”

3. Dr. Vacanti is so open with the media, giving reporters unpublished data, making statements like that his lab has now made human STAP stem cells, and more. This is very unusual for scientists.

2. Not so easy! The STAP method is not working right now in the lab of one of the senior STAP paper authors, Teru Wakayama. He was quoted in Nature News yesterday as saying this method is not easy, which resonates ironically with the original Nature News article on STAP, which said it was an “easy path” to stem cells.

1. Why do the STAP Nature papers not contain methods descriptions sufficient for other labs to reproduce the results? Perhaps as many as a couple dozen people/labs have tried STAP and not gotten it to clearly work. Reportedly a separate methods paper on STAP is in the works by the STAP authors and in theory this should help other labs make STAP work, but why should that be necessary? Shouldn’t the collective methods of a published Nature letter and a Nature article be sufficient for replication?

Do any things about STAP that I haven’t mentioned strike you as particularly weird? Let us all know in the comments.

9 Comments

Hello, Dr. Knoepfler. I’m a complete stranger to this field so excuse me if I’m asking stupid questions. I have two questions.
1.) Is it possible that the authors of the papers are deliberately withholding the crucial information to reproduce the experiment? In that case, is it somehow related to the possible future patent dispute?
2.) Also, in this field, I assume these image duplications are considered serious fabrications. If indeed they were fabricated, could it only be from malice?

> He was quoted in Nature News yesterday as saying this method is not easy, which resonates ironically with the original Nature News article on STAP, which said it was an “easy path” to stem cells. <

This is a classic example when scientists don't know how to write or speak clearly, and other scientists don't bother to understand what they mean.

When they say this method "is not easy" they meant they didn't know which experimental parameters are important, which translates into it sometimes works, sometimes not. It also translates into non-reproducible results.

When they say it was an "easy path" to stem cells, they meant IF they know all the parameters, it wouldn't be too labor intensive or time consuming or requires special skills to duplicate the process.

Regarding point 5: All of the comments on Reddit from the lab member have been deleted; technically this could have been done by the one of the moderators of the sub-reddit, but more likely it was deleted by the user itself.

It appears that the entire user has been removed as well. I don’t think this is an issue involving moderators. It looks like someone started posting anonymously (perhaps as ‘someone else’) to try to generate buzz for the article.

Bad form, really, especially considering all the negative consequences that may well be involved.

I add an 11th weird thing. Man, if I was the team leader of the STAP affair, I would just provide a stap-by-stap protocol to anybody who asks, I would invite selected scientists for STAP training, I would just defend myself oh so loudly to counter all these scientists who dare question the solid method I painstakingly developped.
Instead, what do we get? Zip. No comments. Institute politics is keeping the whole thing under a tight lid, methinks. Maybe the patenting of the method requires silence? Maybe a Nature Method paper is coming? I hope so for all the parties involved.
Weird nonetheless.

Point number 1 is something which really boils my pee (forgive me for being so crude) about many papers published today.

Time was that the constituents of every buffer and the minutae of every step were detailed explicitly right there in the methods of papers. I have become extremely good and knowledgeable about several basic techniques (in situ hybridisation, certain antibody protocols, westerns, northerns, etc) by reading a lot of these older papers which have very slightly different ways of doing the same thing.

Suddenly, around the late 90’s, it became acceptable to merely say “as per manufacturer’s instructions” or “as per protocol”, or simply state antibody epitope name and vendor – but not the cat number, what you block in, how long you incubate for, what concentration you use it at, how you fix, whether you use epitope recovery (and if so how) etc etc. Or even worse, “using a modified protocol from x” – without even hinting at what the modifications are.

It seems utterly laughable that a major nature paper could be published, explicitly presenting results from a NOVEL protocol – without describing that protocol in sufficient detail to be replicated (which is what I’m tempted to think is happening here, rather than fraud). There’s just no way the authors should be allowed to get not one, but several high impact papers detailing the exact same phenomenon due to the absence of sufficient instructions in the first paper. I’d be willing to bet an amount someone else in the lab will go first author on the methods paper – to share the love.

Yes, modern protocols can be a little less robust than more simple protocols by virtue of there being more steps and the field simply being more advanced and trying to do harder things.

However, certain labs even seem to try and obfuscate the methods in such a way as to absolutely require a request to them for a more detailed protocol (I’ve no idea if this is the case here, this isn’t my field, but from what I hear this is rife in the stem cell field). If you publish – it’s in the public domain. So should your methods be. With the move to digital publication, space really isn’t an issue or excuse. How about a PubMethods detailed protocol repository? Although, considering this group even failed to deposit their raw data I wonder how much of a difference that could make.